Bone morphogenetic protein pathway activation, compositions for ossification, and methods related thereto

Abstract

The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair, and methods related thereto. In certain embodiments, the disclosure relates to compositions comprising one or more compound(s) disclosed herein derivatives, or salt thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement. In certain embodiments, compounds disclosed herein are useful for managing obesity and diabetes or other metabolic syndromes by modulation of brown fat.

What we claim: 
     
       1. A method of forming bone or cartilage, comprising implanting a graft composition comprising 5-amino-1H-1, 2, 4-triazole-3-carboxylic acid or an alkyl ester of the carboxylic acid, or salt thereof in a subject wherein bone or cartilage forms in the graft composition. 
     
     
       2. The method of  claim 1 , wherein the graft composition further comprises a bone morphogenetic protein. 
     
     
       3. The method of  claim 1 , wherein the subject has a void in the bony structure wherein the graft composition is implanted in the void. 
     
     
       4. The method of  claim 3 , wherein the void is in a bone selected from an extremity, maxilla, mandible, pelvis, spine and/or cranium. 
     
     
       5. The method of  claim 3 , wherein said void is a result of surgical removal of bone. 
     
     
       6. The method of  claim 1 , further comprising the step of securing movement of bone structure with intramedullary nail fixation, and removing the intramedullary nail after bone forms in the implanted graft. 
     
     
       7. The method of  claim 1 , wherein the 5-amino-1H-1,2,4-triazole-3-carboxylic acid alkyl ester is 5-amino-1H-1,2,4-triazole-3-carboxylic acid, methyl ester. 
     
     
       8. A method of performing spinal fusion, comprising implanting a bone graft composition comprising 5-amino-1H-1,2,4-triazole-3-carboxylic acid or an alkyl ester of the carboxylic acid or salt thereof between two vertebrae of a subject. 
     
     
       9. The method of  claim 8 , wherein the graft composition further comprises a bone morphogenetic protein. 
     
     
       10. A method of growing bone comprising locally administering a pharmaceutical composition to a subject in an area of desired bone growth, wherein the pharmaceutical composition comprises 5-amino-1H-1,2,4-triazole-3-carboxylic acid or an alkyl ester of the carboxylic acid or pharmaceutically acceptable salts thereof. 
     
     
       11. The method of  claim 10 , wherein the administration is through a catheter or hypodermic needle with a tip that is not in a vein.